On March 10, 2020 Proteostasis Therapeutics, Inc. (Nasdaq: PTI), a clinical stage biopharmaceutical company dedicated to the discovery and development of groundbreaking therapies to treat cystic fibrosis (CF) through theratyping, reported financial results for the fourth quarter and full year ended December 31, 2019, and provided a corporate update (Press release, Proteostasis Therapeutics, MAR 10, 2020, View Source [SID1234555383]).

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"Proteostasis made important progress throughout 2019 in delivering on our goal of bringing more treatment choices to patients with CF," said Meenu Chhabra, President and Chief Executive Officer of Proteostasis Therapeutics. "With our Phase 2 trials complete, we are moving forward with a Phase 3 clinical development plan that embraces the pursuit of personalized medicine in CF through theratyping. Our mission is to deliver combinations of our investigational agents to preselected patients identified as responders to our therapies through the ex vivo testing of their own organoids. We believe that the theratyping path, or the process of matching CFTR modulators to individual CF patients based on a laboratory assay regardless of CFTR genotype, has the potential to become a patient-friendly and cost-effective approach to treatment for patients with CF, thereby increasing access to treatment options and optimizing risk-benefit and cost-effectiveness of CFTR modulators."

Ms. Chhabra continued, "Through our next set of clinical trials that may be registrational trials, we will continue to explore the potential of our proprietary CFTR modulators – posenacaftor, dirocaftor and nesolicaftor – in rare and common CF mutations using both traditional and novel study approaches. We look forward to initiating these trials later this year and to providing updates, beginning with the CHOICES trial, soon thereafter."

Fourth Quarter and Recent Highlights

Last month, Proteostasis announced the completion of enrollment of 502 patients with CF in the HIT-CF Europe project, a research project which aims to provide better treatment and improve lives for people with CF and rare mutations. HIT-CF is leading a European-based initiative that is conducting confirmatory trials to assess the predictability of the organoid assay for clinical benefit, such as the CHOICES study (Crossover trial based on Human Organoid Individual response in CF – Efficacy Study). Proteostasis’ drug combinations will be tested first in an ex vivo study expected to be completed in the first half of 2020. Then, responders and non-responders will be selected for the CHOICES study. Dosing in CHOICES is expected to begin in the second half of 2020, with preliminary clinical data anticipated to be reported in early 2021.

In January of this year, Proteostasis announced a regulatory update following the completion of a scientific advice meeting with the Medicines and Healthcare Products Regulatory Agency in the United Kingdom (MHRA) that outlined a path forward for the initiation and execution of our Phase 3 program and the potential filing of a Marketing Authorization Application for posenacaftor, dirocaftor and nesolicaftor. The Company announced that it will continue to seek additional advice from other major regulatory agencies throughout 2020.

In December 2019, Proteostasis announced results from a Phase 2, 28-day clinical trial designed to assess the safety, tolerability and efficacy, of the Company’s once-daily proprietary combinations, 600 mg of posenacaftor (PTI-801) and 300 mg of dirocaftor (PTI-808), with or without 10 mg of nesolicaftor (PTI-428), or placebo. The results demonstrated that the combination was generally well-tolerated in the trial, with the majority of reported adverse events mild to moderate in severity. Homozygous subjects receiving the triple combination experienced a mean absolute improvement in ppFEV1 of 8 percentage points (p ≤ 0.01) and a reduction in sweat chloride concentration of -29 mmol/L (p < 0.0005) at day 28 compared to pooled placebo. In a population with high disease burden, the combination demonstrated compelling improvements in lung function and sweat chloride, including improved outcomes in the most challenging settings, including subjects with at least two pulmonary exacerbations within 12 months prior to study entry.

During the fourth quarter of 2019 through the date of this release, Proteostasis announced several peer-reviewed publications and medical meetings presentations, as well as a Company-hosted event:

In February 2020, the Company co-authored an article, titled "Amplifiers co-translationally enhance CFTR biosynthesis via PCBP1-mediated regulation of CFTR mRNA," which was published in the Journal of Cystic Fibrosis. The publication highlights nonclinical data on the mechanism of action of nesolicaftor (PTI-428).
In January 2020, the Company presented a poster, entitled "Intestinal Organoid Models as a Path for Personalized Therapy Development in Cystic Fibrosis," at the Keystone Symposia on Tissue Organoids. The poster highlighted the results from an ex vivo study of the Company’s proprietary CFTR modulators in organoids from individuals with CF who are ineligible for the current standard of care CFTR modulator therapies due to their genotype, a population of approximately 2,300 adults in Europe alone.
In October 2019, the Company was noted in a presentation highlighting data from the Company’s CF clinical development programs at the North American Cystic Fibrosis Conference that was delivered by Patrick Flume, M.D., Professor of Medicine and Pediatrics, Medical University of South Carolina and Jennifer L. Taylor-Cousar, M.D., M.S.C.S., Associate Professor of Medicine and Pediatrics, and Co-Director and CF Therapeutics Development Network Director of the Adult CF Program at National Jewish Health.
In October 2019, the Company hosted a CF patient summit featuring members of the CF community, including thought leaders, people with CF and CF advocates, and panel discussions focused on current unmet needs in CF.
Year End 2019 Financial Results

Proteostasis reported a net loss of approximately $59.1 million for the year ended December 31, 2019, as compared to a net loss of $61.8 million for the year ended December 31, 2018.

The Company recorded $5.0 million of revenue for the year ended December 31, 2019, as compared to $2.8 million for the same period in the prior year. Revenue for the year ended December 31, 2019 was related to the Company’s agreement with Genentech, Inc., while revenue for the year ended December 31, 2018 was related to the Company’s agreement with Astellas Pharma Inc., which was terminated in the fourth quarter of 2018.

Research and development expenses for the year ended December 31, 2019 were $52.3 million, as compared to $50.3 million for the same period in the prior year. The increase was primarily due to an increase in clinical-related activities.

General and administrative expenses for 2019 were $13.8 million, as compared to $15.7 million for the same period in the prior year. The decrease in general and administrative expenses was due primarily to a decrease in professional fees and facilities-related expenses.

Cash, cash equivalents and short-term investments totaled $69.5 million as of December 31, 2019, compared to $118.4 million as of December 31, 2018. The Company believes that its existing cash, cash equivalents and short-term investments are sufficient to fund operations into the second half of 2021. However, additional funding will be necessary to advance the Company’s proprietary combination therapy candidates through regulatory approval and into commercialization, if approved.

Fourth Quarter 2019 Financial Results

Proteostasis reported a net loss of approximately $11.9 million for the three months ended December 31, 2019, as compared to a net loss of $16.9 million for the same period in the prior year.

There was no revenue in either the three months ended December 31, 2019, or in the same period in the prior year.

Research and development expenses for the three months ended December 31, 2019 were $9.1 million, as compared to $13.7 million for the same period in the prior year. The decrease in research and development expenses for the three months ended December 31, 2019 was primarily due to a decrease in clinical-related activities.

General and administrative expenses for the three months ended December 31, 2019 were $3.1 million, as compared to $3.8 million for the same period in the prior year. The decrease in general and administrative expenses for three months ended December 31, 2019 was due primarily to a decrease in professional fees.

On March 10, 200 AngioDynamics, Inc. (NASDAQ: ANGO), a leading provider of innovative, minimally invasive medical devices for vascular access, peripheral vascular disease, and oncology, reported that it will report financial results for the third quarter of fiscal year 2020 before the market open on Tuesday, April 7, 2020 (Press release, AngioDynamics, MAR 10, 2020, View Source [SID1234555380]). The Company’s management will host a conference call at 8:00 a.m. ET the same day to discuss the results.

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To participate in the conference call, dial 1-877-407-0784 (domestic) or +1-201-689-8560 (international) and refer to the passcode 13700177.

This conference call will also be webcast and can be accessed from the "Investors" section of the AngioDynamics website at www.angiodynamics.com. The webcast replay of the call will be available at the same site approximately one hour after the end of the call.

A recording of the call will also be available from 11:00 a.m. ET on Tuesday, April 7, 2020, until 11:59 p.m. ET on Tuesday, April 14, 2020. To hear this recording, dial 1-844-512-2921 (domestic) or +1-412-317-6671 (international) and enter the passcode 13700177.

On March 10, 2020 McKesson Corporation (NYSE:MCK) reported the completion of the split-off of PF2 SpinCo, Inc. ("SpinCo"), which held McKesson’s interest in Change Healthcare LLC ("Change Healthcare") and which was merged with and into Change Healthcare Inc. (NASDAQ:CHNG) ("Change") through a "Reverse Morris Trust" transaction (Press release, McKesson, MAR 10, 2020, View Source [SID1234555379]). The closing of the merger followed the previously announced expiration of McKesson’s exchange offer. As a result of the merger, participating McKesson stockholders will receive one share of Change common stock in exchange for each whole share of SpinCo common stock they received in the exchange offer.

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"We are pleased to have successfully completed the exit of our investment in Change Healthcare, in line with our stated objective of unlocking value for our shareholders," said Brian Tyler, chief executive officer, McKesson. "We are excited to move forward and execute against our strategic growth initiatives as a more focused organization, and believe McKesson is well positioned with a broad set of differentiated assets and capabilities."

The transactions enabled McKesson to reduce the number of its shares of outstanding common stock by 15,426,537 shares. The exchange offer and merger are expected to be tax-free to participating McKesson stockholders for U.S. federal income tax purposes except to the extent of any cash received in lieu of fractional shares of Change common stock.

McKesson will host a conference call on Tuesday, March 17th at 4:30 PM Eastern Time to discuss the completion of the split-off. A live audio webcast of the conference call will be available on McKesson’s Investor Relations website at View Source The conference call can also be accessed by dialing 786-815-8297. The password is ‘McKesson’.

In connection with the transactions, Goldman Sachs & Co. LLC is acting as financial advisor and Davis Polk & Wardwell LLP is acting as legal advisor to McKesson.

On March 10, 2020 McKesson Corporation (NYSE:MCK) reported that its previously announced offer to stockholders to exchange their shares of McKesson common stock on a per-share-basis for 11.4086 shares of PF2 SpinCo, Inc. ("SpinCo") common stock expired at 11:59 p.m., New York City time, on March 9, 2020, and, based on preliminary results, the exchange offer was oversubscribed (Press release, McKesson, MAR 10, 2020, View Source [SID1234555378]). The exchange offer to split-off SpinCo, which holds McKesson’s interest in Change Healthcare LLC ("Change Healthcare"), is part of McKesson’s agreement with Change Healthcare Inc. (NASDAQ:CHNG) ("Change") to merge SpinCo with and into Change (the "Merger").

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According to the exchange agent for the exchange offer, Equiniti Trust Company, 98,165,418 shares of McKesson common stock were tendered prior to the expiration of the exchange offer, including 65,256,714 shares of McKesson common stock validly tendered and 32,908,704 shares of McKesson common stock that were tendered by notice of guaranteed delivery. McKesson has accepted 15,426,537 of the tendered shares of McKesson common stock in exchange for 175,995,192 shares of SpinCo common stock.

Immediately following the consummation of the exchange offer, and by means of the merger of SpinCo with and into Change, each outstanding share of SpinCo common stock will be converted into one share of Change common stock (with cash in lieu of fractional shares).

Because the exchange offer was oversubscribed, McKesson accepted tendered shares of McKesson common stock on a pro rata basis in proportion to the total number of shares tendered and not validly withdrawn. Stockholders who owned fewer than 100 shares of McKesson common stock, or an "odd lot," and who validly tendered all of their shares are not subject to proration in accordance with the terms of the exchange offer.

Based on the total number of shares of McKesson common stock that were reported as tendered prior to the expiration of the exchange offer, it is estimated that approximately 14.70% of the tendered shares of McKesson common stock that are subject to proration will be exchanged for shares of SpinCo common stock, assuming all shares tendered by guaranteed delivery procedures are delivered under the terms of the exchange offer. The preliminary proration factor is subject to change based on the number of tendered shares that satisfy the guaranteed delivery procedures.

McKesson expects to announce the final proration factor as soon as possible following the expiration of the guaranteed delivery period, which will occur on March 11, 2020. Promptly after the final proration factor is announced, shares of McKesson common stock tendered but not accepted for exchange will be returned to the tendering stockholders in book-entry form. Also at that time, the exchange agent for the exchange offer will deliver to Change’s transfer agent a final stockholder list for SpinCo common stock to be received by tendering McKesson stockholders whose shares were accepted for exchange in the exchange offer. Change’s transfer agent will use the final stockholder list to credit such tendering McKesson stockholders with whole shares of Change common stock. Fractional shares of Change common stock deliverable to tendering McKesson common stock holders will be aggregated and sold in the open market by Change’s transfer agent, or otherwise as reasonably directed by McKesson within 20 business days after the effective time of the Merger. Checks in lieu of fractional shares will thereafter be delivered to such tendering McKesson common stock stockholders by Change’s transfer agent, after deducting any required withholding taxes and brokerage charges, commissions and transfer taxes, on a pro rata basis, without interest, as soon as practicable.

In connection with the transactions, Goldman Sachs & Co. LLC is acting as financial advisor and Davis Polk & Wardwell LLP is acting as legal advisor to McKesson.

On March 10, 2020 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported the results from the TOURMALINE-MM2 study designed to evaluate the addition of NINLARO (ixazomib) to lenalidomide and dexamethasone in newly diagnosed transplant ineligible multiple myeloma patients (Press release, Takeda, MAR 10, 2020, View Source [SID1234555377]). The addition of ixazomib to lenalidomide and dexamethasone resulted in an improvement in median progression-free survival (PFS) of 13.5 months (35.3 months versus 21.8 months; hazard ratio [HR] 0.83; p=0.073); however, it did not meet the threshold for statistical significance. The safety profile associated with NINLARO from the TOURMALINE-MM2 trial was generally consistent with the existing prescribing information.

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Results from the TOURMALINE-MM2 study will be submitted to an upcoming medical congress.

"There is a need for treatment options in transplant ineligible patients. We remain committed to advancing the field of multiple myeloma and continue to drive innovation through ongoing research and development," said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. "We are confident there will be numerous learnings from this trial and look forward to sharing these data with the community. We want to thank the patients and investigators for their participation in this important program."

Investigators have been informed of the outcome and will discuss the potential impact with study participants. For patients currently enrolled in this study, it is up to the discretion of physicians to continue their current treatment.

About the TOURMALINE-MM2 Trial

TOURMALINE-MM2 is an international, randomized, double-blind, multicenter, placebo-controlled Phase 3 clinical trial, designed to evaluate NINLAROTM (ixazomib) plus lenalidomide and dexamethasone compared to placebo plus lenalidomide and dexamethasone, in 705 adult patients with newly diagnosed multiple myeloma who are not candidates for transplant. The primary endpoint is progression-free survival (PFS). Key secondary endpoints include rate of complete response (CR), pain response and overall survival (OS). For additional information: View Source

About Multiple Myeloma

Multiple myeloma is a life-threatening rare blood cancer that arises from the plasma cells, a type of white blood cell that is made in the bone marrow. These plasma cells become abnormal, multiply and release a type of antibody known as a paraprotein, which causes symptoms of the disease, including bone pain, frequent or recurring infections and fatigue, a symptom of anemia. These malignant plasma cells have the potential to affect many bones in the body and can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count. The typical multiple myeloma disease course includes periods of symptomatic myeloma followed by periods of remission. Nearly 230,000 people around the world live with multiple myeloma, with approximately 114,000 new cases diagnosed globally each year.

About NINLAROTM (ixazomib) capsules

NINLARO (ixazomib) is an oral proteasome inhibitor which is being studied across the continuum of multiple myeloma treatment settings. NINLARO was first approved by the U.S. Food and Drug Administration (FDA) in November 2015 and is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. NINLARO is currently approved in more than 60 countries, including the United States, Japan and in the European Union, with more than 10 regulatory filings currently under review. It was the first oral proteasome inhibitor to enter Phase 3 clinical trials and to receive approval.

NINLAROTM (ixazomib): GLOBAL IMPORTANT SAFETY INFORMATION

SPECIAL WARNINGS AND PRECAUTIONS

Thrombocytopenia has been reported with NINLARO (28% vs. 14% in the NINLARO and placebo regimens, respectively) with platelet nadirs typically occurring between Days 14-21 of each 28-day cycle and recovery to baseline by the start of the next cycle. It did not result in an increase in hemorrhagic events or platelet transfusions. Monitor platelet counts at least monthly during treatment with NINLARO and consider more frequent monitoring during the first three cycles. Manage with dose modifications and platelet transfusions as per standard medical guidelines.

Gastrointestinal toxicities have been reported in the NINLARO and placebo regimens respectively, such as diarrhea (42% vs. 36%), constipation (34% vs. 25%), nausea (26% vs. 21%), and vomiting (22% vs. 11%), occasionally requiring use of antiemetic and anti-diarrheal medications, and supportive care.

Peripheral neuropathy was reported with NINLARO (28% vs. 21% in the NINLARO and placebo regimens, respectively). The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.

Peripheral edema was reported with NINLARO (25% vs. 18% in the NINLARO and placebo regimens, respectively). Evaluate patients for underlying causes and provide supportive care, as necessary. Adjust the dose of dexamethasone per its prescribing information or the dose of NINLARO for severe symptoms

Cutaneous reactions occurred in 19% of patients in the NINLARO regimen compared to 11% of patients in the placebo regimen. The most common type of rash reported in both regimens was maculo-papular and macular rash. Manage rash with supportive care, dose modification or discontinuation.

Thrombotic microangiopathy, sometimes fatal, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), have been reported in patients who received NINLARO. Monitor for signs and symptoms of TPP/HUS and stop NINLARO if diagnosis is suspected. If the diagnosis of TPP/HUS is excluded, consider restarting NINLARO. The safety of reinitiating NINLARO therapy in patients previously experiencing TPP/HUS is not known.

Hepatotoxicity, drug-induced liver injury, hepatocellular injury, hepatic steatosis, and hepatitis cholestatic have been uncommonly reported with NINLARO. Monitor hepatic enzymes regularly and adjust dose for Grade 3 or 4 symptoms.

Pregnancy- NINLARO can cause fetal harm. Advise male and females patients of reproductive potential to use contraceptive measures during treatment and for an additional 90 days after the final dose of NINLARO. Women of childbearing potential should avoid becoming pregnant while taking NINLARO due to potential hazard to the fetus. Women using hormonal contraceptives should use an additional barrier method of contraception.

Lactation- It is not known whether NINLARO or its metabolites are excreted in human milk. There could be potential adverse events in nursing infants and therefore breastfeeding should be discontinued.

SPECIAL PATIENT POPULATIONS

Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.

Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease (ESRD) requiring dialysis. NINLARO is not dialyzable and, therefore, can be administered without regard to the timing of dialysis.

DRUG INTERACTIONS

Co-administration of strong CYP3A inducers with NINLARO is not recommended.

ADVERSE REACTIONS

The most frequently reported adverse reactions (≥ 20%) in the NINLARO regimen, and greater than in the placebo regimen, were diarrhea (42% vs. 36%), constipation (34% vs. 25%), thrombocytopenia (28% vs. 14%), peripheral neuropathy (28% vs. 21%), nausea (26% vs. 21%), peripheral edema (25% vs. 18%), vomiting (22% vs. 11%), and back pain (21% vs. 16%). Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more of the three drugs was discontinued in ≤ 1% of patients in the NINLARO regimen.